DESCRIPTION: The lack of durability of resin-dentin bonds results in enormous health care costs as tooth-colored restorations require frequent replacement due to deteriorating interfacial coupling of resin composites to dentin. Our overall hypothesis is that the lack of durability involves degradation of both the resin and collagen phases of the hybrid layer that creates the interracial coupling. Due to the wet bonding technique, adhesive formulations are more hydrophilic than in the past. Hydrophilic resins in the adhesive promote nonuniform water absorption that creates water-filled voids and channels that accelerate hydrolysis of ester bonds in the polymers. We propose to follow the rate of these processes nondestructively by measuring changes in the electrical impedance of resins. Long-term bonding studies in vitro and in vivo show the loss of collagen from the hybrid layer. Collagen fibrils in the dentin matrix appear to be hydrolyzed in vitro, even in the absence of bacteria, by matrix metalloproteinases (MMPs) that were trapped in the matrix during its formation, and that slowly attack the demineralized collagen fibrils infiltrated with resin. This overall hypothesis will be tested by experiments designed to contrast the stability of hydrophilic versus hydrophobic resins; we will also test the stability of collagen matrices when they are fully demineralized versus when they are bonded to demineralized matrices that are within 10 um of mineralized dentin that can slowly expose more MMPs, or when MMPs in dentin are inactivated by heat or enzyme inhibitors. A variety of inhibitors of MMPs will be tested to determine if they can prevent the loss of the mechanical properties of the matrix that leads to low bond strengths and coupling failures. Hopefully, a nonspecific inhibitor of MMP (e.g. chlorhexidine or bisphosphonates) can be applied as a pretreatment during bonding or incorporated into bonding resins to greatly improve the durability of resin-dentin bonds. Alternative approaches such as the use of fluoride-containing resins will be evaluated in an attempt prevent matrix demineralization that we believe is responsible for the exposure of MMPs from the underlying mineralized matrix. This comprehensive approach to improving the durability of resin-dentin bonds should ultimately save billions of dollars in health care and much human suffering.